DNA segment containing C beta 1, a gene for the constant region of the beta chain of the T-cell antigen receptor, was inserted into chromosome 6 in cells from one patient with human T-cell leukemia.
DNA rearrangements that occurred in the vicinity of T-cell antigen receptor beta-chain gene clusters residing on chromosome 7 were examined in human T-cell acute lymphoblastic leukemia cells. In one patient, it was observed that, for the T-cell receptor beta-chain genes, a D beta 1-J beta 2.3 (where D is diversity and J is joining) junction was found on one chromosome, while the other chromosome kept the germ-line configuration. If this D beta-J beta junction was formed by the customary deletion mechanism, the C beta 1 gene (where C is constant) located between the D beta 1 and J beta 2.3 loci should have disappeared from this chromosome. The C beta 1 gene indeed was absent from the rearranged chromosome 7, but it was found on chromosome 6 as an inserted segment. The implications of the observations are discussed.


Carnitine level and several lipid parameters in venous blood of newborns, cord blood and maternal blood and milk.
To obtain a rather complex picture on fat metabolism in newborns, fundamental characteristics of this metabolism as well as the carnitine level in their blood was correlated with corresponding values from cord blood, maternal blood and milk. The concentrations of cholesterol (CHOL), triglycerides (TGL) and apolipoprotein B (Apo-B) in 4 days old infants were higher than in cord blood (P < 0.01 and P < 0.001, resp.), but were only 50% of those in blood of the respective mothers. No differences in HDL-CHOL were observed, whereas the level of apolipoprotein A (Apo-A) in cord blood exceeded that in newborn blood (P < 0.05). The level of carnitine in milk was about twice as high as in maternal blood (P < 0.001) which was the consequence of the high acylcarnitine content in milk. Our results represent a basis for comparison of normal and pathologically altered metabolic situation, e.g. in hypotrophic newborns and potentially in newborns in need of parenteral nutrition.


A Comprehensive Survey of Institutional Patient/Family Educational Practices for Newly Diagnosed Pediatric Oncology Patients.
Patient/family education is an important component of nursing practice and is essential to the care of children newly diagnosed with cancer. Practices regarding patient/family education in Children's Oncology Group (COG) treatment centers have not been well described. We used an Internet-based survey to determine current patient/family educational practices at COG institutions; participation rate was 90.5% (201/222). Patient/family education was delivered primarily by an individual (rather than a team) at 43% of institutions. Advanced practice nurses had primary responsibility for providing education at 32% of institutions. "Fever" was the most frequently reported topic considered mandatory for inclusion in education for newly diagnosed patients. More than half of institutions reported using checklists and/or end-of-shift reports to facilitate health care team communication regarding patient/family education, and 77% reported using the "teach-back" method of assessing readiness for discharge. Thirty-seven percent of institutions reported delays in hospital discharge secondary to the need for additional teaching. An understanding of current practices related to patient/family education is the first step in establishing effective interventions to improve and standardize educational practices in pediatric oncology.


MiR-449a suppresses the epithelial-mesenchymal transition and metastasis of hepatocellular carcinoma by multiple targets.
Increasing evidence indicates that Epithelial-mesenchymal transition (EMT) can be regulated by microRNAs (miRNAs). MiR-449a is a liver abundant miRNA. However, the role of miR-449a in the metastasis of hepatocellular carcinoma (HCC) remains largely unknown. The expression levels of miR-449a were first examined in HCC cell lines and tumour tissues by real-time PCR. The in vitro and in vivo functional effect and underlying molecular mechanisms of miR-449a were examined further. In the present study, we found that miR-449a was significantly decreased in HCC cells and tissues, especially in those with the portal vein tumor thrombus. In HCC cell lines, stable overexpression of miR-449a was sufficient to inhibit cell motility in vitro, and pulmonary metastasis in vivo. In addition, ectopic overexpression of miR-449a in HCC cells promoted the expression of epithelial markers and reduced the levels of mesenchymal markers. Further studies revealed that the reintroduction of miR-449a attenuated the downstream signaling of Met, and consequently reduced the accumulation of Snail in cell nucleus by targeting the 3'-untranslated regions (3'-UTR) of FOS and Met. Our data highlight an important role of miR-449a in the molecular etiology of HCC, and implicate the potential application of miR-449a in cancer therapy.


Lymphocyte and cytokines after short periods of exercise.
The purpose of this study was to verify the effects of short periods of exercise of different intensity on lymphocyte function and cytokines. Thirty Wistar rats, 2 months old, were used. They were divided into five groups of six rats: a sedentary control group; a group exercised for 5 minutes at low intensity (5 L); a group exercised for 15 minutes at low intensity (15 L); and groups exercised at moderate intensity (additional load of 5 % of body weight) for 5 minutes (5 M) or for 15 minutes (15 M). The parameters measured were: total leukocytes, neutrophils, lymphocytes, monocytes, lymphocytes from lymph nodes, serum cytokines (IL-2, IL-6 and TNF-alpha), lymphocyte mitochondrial transmembrane potential, viability and DNA fragmentation. ANOVA two way followed by Tukey's post hoc test (p <or= 0.05) was used. The exercised groups exhibited a significant increase in total leukocytes, tissue and circulating lymphocytes in comparison with the control group. There was a significant decrease in lymphocyte viability and decrease in DNA fragmentation for the 15 M group when compared with the control. There was a decrease in the level TNF-alpha in the 5 M and 15 M groups. Short-term, low- and moderate-intensity exercise may be considered for sedentary individuals beginning to exercise, since no deleterious alterations were observed in lymphocyte function.


Atrial repolarization in healthy males. Studies with programmed stimulation and monophasic action potential recordings.
Right atrial effective refractory periods (AERP) and monophasic action potentials (MAP) have been determined in 29 healthy males in four different age groups between 25 and 64 years. One age group (45-54 years) showed a significantly longer AERP than the others, with a mean of 283 msec compared with 230-238 msec in the other groups. However, no age trend was found in the total material. The AERP decreased at higher paced heart rates, the decrease between paced cycle lengths of 800 and 600 msec amounting to 13 msec. When the MAP and the AERP were determined in the same position of the atrium, they showed no statistically significant correlation. A possible explanation is that the cells contributing to the AERP and the MAP are not altogether the same. The MAP and the AERP determinations have a similar degree of reproducibility but possibly mirror different kinds of repolarization phenomenon.


Genetic similarity and mate selection in Uruguay.
It has been suggested that average genetic similarity, as assessed by blood genetic markers, could influence mate choice in humans. In the present study, average genetic similarity was assessed in 183 couples submitting to paternity determinations in relation to six blood group systems and three HLA loci. Couples in which the putative father was excluded were compared with those in which such exclusion did not occur, and real couples were compared to random pairs. The differences were all statistically nonsignificant. Possible reasons for the different results found in the previous sample and in the present study are considered.


Soft and hard tissue response to an implant with a convergent collar in the esthetic area: preliminary report at 18 months.
The purpose of this prospective cohort study was to investigate, over an 18-month period, soft and hard tissue response to a transmucosal implant with a convergent collar inserted in the anterior maxillary esthetic area. From June 2013 to January 2014, 14 consecutive patients were enrolled (7 men and 7 women; mean age 63.7 ± 14 years) with 20 implants, needing at least one implant-supported restoration between the canines in the maxillary anterior esthetic area. Six months after hopeless tooth extraction and an alveolar socket graft, a transmucosal-type implant with convergent collar walls was inserted in a midcrestal position with mini-flap surgery. An impression was taken 2 months later, and a definitive abutment with a provisional restoration was positioned. The final restoration was seated 2 weeks later. Clinical parameters, photographs, radiographs, and impressions were taken at this timepoint, and after 6 and 18 months. Using dedicated software, radiographic analysis (to detect marginal bone-level changes) and cast analysis (to detect soft tissue vertical and horizontal changes) were performed. At the 18-month follow-up, all implants were clinically osseointegrated, stable, and showed no sign of infection. At baseline, interproximal radiographs revealed no bone defect around the implant. After an initial minimal bone loss (0.09 ± 0.144 mm), radiographic analysis showed a stable condition of bone remodeling (mean value 0.09 ± 0.08; range 0.0 to 0.5 mm) at the 18-month follow-up. No statistically significant horizontal dimensional changes of the alveolar ridge were observed between each timepoint. Mean soft tissue levels significantly improved between baseline and 18 months. The mean heights of the mesial papilla (MP) and distal papilla (DP) changes were 0.38 ± 0.22 and 0.47 ± 0.31, respectively. The level of the labial gingival margin (LGM) was 1.01 ± 0.63. Periodontal parameters never exceeded the physiological levels. Within the limitations of this preliminary study, the analyzed implants produced positive results in these esthetically demanding cases. This outcome should encourage long-term studies in order to assess, through controlled clinical trials, whether this convergent collar design offers advantages over other designs. Furthermore, due to the peculiar crestal module, together with the use of delayed implant insertion and a postextraction ridge preservation technique with biomimetic hydroxyapatite, the analyzed implants seem to help prevent the negative bone remodeling typically associated with two-piece implant systems, but without the well-known drawbacks of traditionally designed transmucosal implants. Therefore, wherever crestal bone preservation is a critical issue for clinical success in the anterior maxillary area can be considered of particular interest.


The ancillary N-terminal region of the yeast AP-1 transcription factor Yap8 contributes to its DNA binding specificity.
Activator protein 1 (AP-1) is one of the largest families of basic leucine zipper (bZIP) transcription factors in eukaryotic cells. How AP-1 proteins achieve target DNA binding specificity remains elusive. In Saccharomyces cerevisiae, the AP-1-like protein (Yap) family comprises eight members (Yap1 to Yap8) that display distinct genomic target sites despite high sequence homology of their DNA binding bZIP domains. In contrast to the other members of the Yap family, which preferentially bind to short (7-8 bp) DNA motifs, Yap8 binds to an unusually long DNA motif (13 bp). It has been unclear what determines this unique specificity of Yap8. In this work, we use molecular and biochemical analyses combined with computer-based structural design and molecular dynamics simulations of Yap8-DNA interactions to better understand the structural basis of DNA binding specificity determinants. We identify specific residues in the N-terminal tail preceding the basic region, which define stable association of Yap8 with its target promoter. We propose that the N-terminal tail directly interacts with DNA and stabilizes Yap8 binding to the 13 bp motif. Thus, beside the core basic region, the adjacent N-terminal region contributes to alternative DNA binding selectivity within the AP-1 family.


[Sensory transplants of the sole of the foot].
The covering of defects of the sole of the foot and the heel with pedicled and free neurovascular flaps such as the dorsalis pedis flap, the forearm flap and the pulp neurovascular flap shows good success because of early pain sensation re-ulceration can be prevented. Clinical cases are demonstrated.


Environmental DNA and visual encounter surveys for amphibian biomonitoring in aquatic environments of the Ecuadorian Amazon.
The development of anthropogenic activities has generated a decline in aquatic fauna populations, and amphibians have been the most affected. The decline of batrachofauna is concerning, as 41% of all species worldwide are endangered. For this reason, rapid, efficient, and non-invasive biodiversity monitoring techniques are needed, and environmental DNA (eDNA) is one such tool that has been sparsely applied in Ecuador. This technique has allowed scientists generates information on species diversity and amphibian community composition from a water sample. This study applied eDNA-based biomonitoring analyses and visual encounter surveys (VES) as inventory techniques to identify the diversity of aquatic amphibians in the Tena River micro-basin (TRMB). The experimental design was divided into three components: (1) fieldwork: all amphibians were recorded by the VES technique and water samples were collected; (2) laboratory work: DNA isolation from amphibian tissue samples and eDNA-containing filters, amplification, electrophoresis, and sequencing were performed; (3) Data analysis: a local DNA reference database was constructed, and eDNA sequence data were processed for classification, taxonomic assignment, and ecological interpretation. Using both eDNA and VES, we detected 33 amphibian species (13 with eDNA only, five with VES only, and 15 with both methods). These species belonged to six amphibian families: Hylidae being the richest with 14 species (three eDNA, one VES, and 10 with both methods), followed by Strabomantidae with nine species (six eDNA, one VES, and two with both methods). All families were detected with both methods, except for the Aromobatidae, having one single record (Allobates aff. insperatus) by VES. Individually, eDNA detected 28 species and had a detection probability (DP) of 0.42 CI [0.40-0.45], while VES recorded 20 species with a DP of 0.17 CI [0.14-0.20]. Similarly, using VES, Cochranella resplendens was detected for the first time in TRMB, while with eDNA, four mountain frogs Pristimantis acerus, Pristimantis eriphus, Pristimantis mallii, and Pristimantis sp. (INABIO 15591) previously recorded at 1,518 m.a.s.l. at altitudes below 600 m.a.s.l. were detected. Results obtained in this study showed that eDNA-based detection had a greater capacity to detect amphibians in aquatic environments compared to VES. The combination of VES and eDNA improves the sensitivity of species detection and provides more reliable, robust, and detailed information. The latter is essential for developing conservation strategies in the Ecuadorian Amazon.


Clinicopathological correlations in aphasiology by means of computerized axial tomography: interest of using printout and prospective considerations.
This study was undertaken following a first paper describing cerebral clinicopathological correlations in aphasiology using computerized axial tomography. Its originality lies in the fact that we studied the correlations starting from the lesional sites and deducing the aphasiologic diagnosis. Our conclusions are similar but show that a small proportion of the patients do not follow the usual pattern of correlations. In view of future prospective studies, the authors emphasize the importance of information to analyze and compare well-individualized clinical syndromes. We suggest that such clinicopathological correlations could be used in other fields of neuropsychology.


Hydrolyzed Chicken Meat Extract Attenuates Neuroinflammation and Cognitive Impairment in Middle-Aged Mouse by Regulating M1/M2 Microglial Polarization.
Aging is the most common cause of several neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease. The pathological hallmarks of age-dependent neuropathology consist of chronic neuroinflammation, oxidative stress, gliosis, learning disability, and cognitive decline. A novel hydrolyzed bioactive peptide mixture extracted from chicken meat, that is, hydrolyzed chicken extract (HCE) has been previously demonstrated to exert neuroprotective effects in rodents and humans. However, the mechanism of HCE on age-related neurological disorders remains unclear. Herein, we aimed to clarify the impact and mechanism of isolated bioactive components (BCs) from HCE on age-dependent neuroinflammation and cognitive impairment in middle-aged mice. We found that both BC and HCE supplementation ameliorated age-induced memory loss, alleviated hippocampal neuroinflammation and oxidative stress, followed by promoting hippocampal neurogenesis in mice. BC and HCE treatment also ameliorated age-dependent morphological anomalies and alleviated microgliosis and astrogliosis. In parallel, BC and HCE treatment showed a significant decrease in the NF-κB p65 and p38 MAPK signaling, which were associated with the enhancement of antioxidative enzymes activities. Furthermore, BC treatment attenuated the neuroinflammatory phenotypes by the decrease in M1-polarized microglia and the increase in M2-polarized microglia in vivo and in vitro. In addition, we found that cyclo(Phe-Phe), one of the cyclopeptides purified from BC, showed notable anti-inflammatory effects in BV2 cells. Taken together, BC might be used as a dietary supplement for alleviating age-dependent neuropathology in middle-aged individuals.


Silencing JA hydroxylases in Nicotiana attenuata enhances jasmonic acid-isoleucine-mediated defenses against Spodoptera litura.
Jasmonic acid (JA) plays important roles in plant resistance to insect herbivores. One important derivative of JA is 12-OH-JA, which is produced by two independent pathways: direct hydroxylation of JA by jasmonate-induced oxygenases (JOXs) or hydrolyzation of 12-OH-JA-Ile.Yet the function of 12-OH-JA in plant-herbivore interactions remains largely unknown. In this study, we silenced four JOX homologs independently in the wild tobacco Nicotiana attenuata by virus-induced gene silencing (VIGS), and found that all four JOX homologs are involved in JA hydroxylation. Simultaneously silencing the four JA hydroxylases in VIGS-NaJOXs plants decreased herbivory-induced 12-OH-JA by 33%, but JA and JA-Ile levels increased by 45% and 30%, respectively, compared to those in control plants. Compared to direct hydroxylation from JA, hydrolyzation from 12-OH-JA-Ile is equally important for herbivory-induced 12-OH-JA accumulation: in the 12-OH-JA-Ile deficient irJAR4/6 plants, 12-OH-JA decreased 34%. Moreover, VIGS-NaJOXs plants exhibited enhanced resistance to the generalist herbivore Spodoptera litura. The poor larval performance was strongly correlated with high levels of several JA-Ile-dependent direct defense metabolites in the VIGS-NaJOXs plants. When we simultaneously silenced all four JA hydroxylases in the JA-Ile-deficient irJAR4/6 background, the enhanced herbivore resistance diminished, demonstrating that enhanced herbivore resistance resulted from elevated JA-Ile levels. Given that silencing these NaJOX-like genes did not detectably alter plant growth but highly increased plant defense levels, we propose that JOX genes are potential targets for genetic improvement of herbivore-resistant crops.


Gene transcription and chromatin regulation in hypoxia.
Oxygen sensing is an essential feature of metazoan biology and reductions in oxygen availability (hypoxia) have both physiological and pathophysiological implications. Co-ordinated mechanisms have evolved for sensing and responding to hypoxia, which involve diverse biological outputs, with the main aim of restoring oxygen homeostasis. This includes a dynamic gene transcriptional response, the central drivers of which are the hypoxia-inducible factor (HIF) family of transcription factors. HIFs are regulated in an oxygen-dependent manner and while their role in hypoxia is well established, it is apparent that other key players are required for gene expression control in hypoxia. In this review, we highlight the current understanding of the known and potential molecular mechanisms underpinning gene transcriptional responses to hypoxia in mammals, with a focus on oxygen-dependent effects on chromatin structure.


Rapid and Low-Cost CRP Measurement by Integrating a Paper-Based Microfluidic Immunoassay with Smartphone (CRP-Chip).
Traditional diagnostic tests for chronic diseases are expensive and require a specialized laboratory, therefore limiting their use for point-of-care (PoC) testing. To address this gap, we developed a method for rapid and low-cost C-reactive protein (CRP) detection from blood by integrating a paper-based microfluidic immunoassay with a smartphone (CRP-Chip). We chose CRP for this initial development because it is a strong biomarker of prognosis in chronic heart and kidney disease. The microfluidic immunoassay is realized by lateral flow and gold nanoparticle-based colorimetric detection of the target protein. The test image signal is acquired and analyzed using a commercial smartphone with an attached microlens and a 3D-printed chip-phone interface. The CRP-Chip was validated for detecting CRP in blood samples from chronic kidney disease patients and healthy subjects. The linear detection range of the CRP-Chip is up to 2 μg/mL and the detection limit is 54 ng/mL. The CRP-Chip test result yields high reproducibility and is consistent with the standard ELISA kit. A single CRP-Chip can perform the test in triplicate on a single chip within 15 min for less than 50 US cents of material cost. This CRP-Chip with attractive features of low-cost, fast test speed, and integrated easy operation with smartphones has the potential to enable future clinical PoC chronic disease diagnosis and risk stratification by parallel measurements of a panel of protein biomarkers.


[Functiono-morphologic characteristics of tissue basophils of the human skin based on electron microscopic data].
A study is presented of the ultrastructure of tissue basophils evaluated by electron microscopy in patients with rheumatism and rheumatoid arthritis. Four types of cells were distinguished according to their functional activity and morphological manifestations. Qualitative analysis of the population of tissue basophils allows to establish a relationship with such characteristics of the clinical picture as activity of the inflammatory process primarily and to analyze in detail the role and significance of these cell forms in the process of formation of inflammatory changes in the connective tissue.


Sensitivities of strains of enteropathogenic Escherichia coli to cephalexin and other antibiotics.
The sensitivity patterns of strains of enteropathogenic Escherichia coli to nine antibiotics were determined. Most strains were sensitive to gentamicin, kanamycin, neomycin, and colistin. Sensitivity to cephalexin was generally greater than sensitivity to ampicillin. Compared with sensitivity patterns of strains isolated in previous years, no significant change in sensitivity patterns of recently isolated strains was detected. All ampicillin-resistant strains destroyed the drug by producing beta-lactamase. The activity of this enzyme against cephalexin was significantly lower than its activity against ampicillin. The role of beta-lactamase, the correlation between its production and resistance to beta-lactamase antibiotics, and the similarity between beta-lactamase produced by EEC and the classified beta-lactamases produced by other enteric bacteria and Escherichia coli, are discussed.


Limb-Shaking And Transient Ischemic Attack: A Systematic Review.
Limb-shaking is one of the transient ischemic attacks (TIA) 'chameleons.' This literature review aims to evaluate the clinical, epidemiological profile, pathologic mechanisms, and management of limb-shaking TIA. Relevant reports in Medline's (PubMed) database were identified and assessed by 2 reviewers without language restriction from 1985 to 2022. A total of 82 reports containing 161 cases that developed limb-shaking TIA were reported. The mean and median age were 61.36 (SD: 15.29) and 62 years (range: 4-93 y). Most of the individuals affected were males (64.34%). Limb-shaking was reported as unilateral in 83.33% of the patients. Limb-shaking presented with other neurological deficits in 44.33% of the individuals, in which the most common concurrent neurological deficit was the weakness of at least 1 limb. A recurrence of the "shaking" phenomenon was observed in 83 individuals. A trigger of limb-shaking was reported in 69 cases, and the most common was changing body position. The internal carotid artery was the most frequent vessel involved in limb-shaking. A chronically occluded internal carotid artery was observed in 42 individuals. Hypertension was the most common comorbidity. The management was conservative in 42.30% of the cases. The most frequent misdiagnoses were seizures. A full recovery was achieved in 56.60% of the individuals. Limb-shaking TIA could be defined as involuntary, rhythmic, brief (<5 min), recurrent, jerky movement usually precipitated by activities that may reduce cerebral blood flow. The "shaking" phenomenon was primarily described as a manifestation of symptomatic complete internal carotid artery obstruction.


Comparison of Short-Term Complications of General and Spinal Anesthesia for Primary Unilateral Total Knee Arthroplasty.
To compare the occurrences of perioperative complications of two anesthetic techniques (general anesthesia [GA] and spinal anesthesia [SA] in patients undergoing primary unilateral total knee arthroplasty (TKA). Patients who underwent unilateral primary TKA due to osteoarthritis from January 2005 to January 2014 were retrospectively reviewed. They were divided into two groups: GA (n=490) and SA (n=746). The operation duration, length of perioperative stay in the operation room and occurrences of adverse events in postoperative 30 days (mean, 29.7±3.1 days) were compared. Before multivariate linear or logistic regression analysis, different baseline characteristics were adjusted in the statistical models. There were significant intergroup differences in mean age (GA, 68.4±7.2 years; SA, 70.7±7.5 years; p<0.001) and mCCI (GA, 3±1.4; SA, 3.2±1.5; p<0.001). The GA group required longer preoperative room time (+9.4 minutes; p<0.001), postoperative room time (+12.7 minutes; p<0.001), and postoperative hospital stay (+2.5 days; p=0.001) and had more surgical site infections (5 [1%] vs. 0 [0%]; p=0.005) and blood transfusion (205 [41.8%] vs. 262 [35.1%]; p=0.01). No differences in operative duration and other adverse events were identified. We should cautiously consider that GA may be associated with slightly increased preoperative and postoperative room times, postoperative hospital stay, transfusion and surgical site infection rates in primary unilateral TKA.


The status of evidence-based medicine education in urology residency.
Evidence-based medicine (EBM) is the conscientious, explicit, and judicious use of the current best evidence in decision-making for the care of patients. Teaching best evidence practice in residency should include both formal or freestanding content, as well as integration into clinical scenarios and patient care. We sought to assess the attitudes, experience and knowledge of EBM in urology residency training across Canada. An anonymous, cross-sectional, self-report questionnaire was completed by a convenience sample of 29 residents, including all chief urology residents in English-speaking programs across Canada. The survey included both open-ended and closed-ended questions designed to assess familiarity and attitudes towards EBM and potential barriers to developing EBM skills in a surgical training program. Questions were formatted to determine the understanding of statistical and analytical concepts, as well as familiarity of available EBM resources. Descriptive and correlative statistics were used to analyze the responses. The response rate was 100%. An overwhelming majority of residents felt that EBM is an important component of the urology residency and journal club was the most common vehicle for discussing best evidence concepts. However, there was significant variation in the presence of freestanding, formal curricula across programs, with only 28% of residents signifying that they received any formal training in their program. The apparent level of understanding of important EBM terminology and resources appears to be limited. The most frequently stated barriers to incorporating EBM curricula into urology training were time constraints and a perceived lack of expert educators. This self-report survey of urology chief residents identified the overwhelming acceptance of the importance of EBM in their training. Although best evidence practices appears to be addressed in journal clubs and in real-life clinical experiences, the obvious lack of familiarity and understanding of EBM content and resources would suggest a need for redoubling efforts to ensure appropriate exposure and instruction in our training programs.


Regulation of the host immune system by helminth parasites.
Helminth parasite infections are associated with a battery of immunomodulatory mechanisms that affect all facets of the host immune response to ensure their persistence within the host. This broad-spectrum modulation of host immunity has intended and unintended consequences, both advantageous and disadvantageous. Thus the host can benefit from suppression of collateral damage during parasite infection and from reduced allergic, autoimmune, and inflammatory reactions. However, helminth infection can also be detrimental in reducing vaccine responses, increasing susceptibility to coinfection and potentially reducing tumor immunosurveillance. In this review we will summarize the panoply of immunomodulatory mechanisms used by helminths, their potential utility in human disease, and prospective areas of future research.


Lung volume reduction surgery: answering the crucial questions.
Emphysema and other forms of COPD are not only common, but also have a poor prognosis. Mortality with severe COPD may be as high as 60% at 5 years and is associated with a significant degree of disability and cost to the health-care system. Building on Dr. Otto Brantigan's experience in the 1950s, when multiple-wedge resections of emphysematous lung were performed to decrease lung volume, thereby improving airflow and reducing hyperinflation, recent investigators, utilizing improved surgical and anesthetic technique, have redeveloped a surgical approach to the treatment of emphysema. The operations used to treat emphysema include excision of large bullae (bullectomy) and resection of diffusely emphysematous lung and are variously known as lung volume reduction surgery (LVRS), pneumectomy, and reduction pneumoplasty. These operations aim for a 20 to 30% reduction in lung volume and may be performed by stapler or laser resection, or both. The mechanisms of benefit have been attributed to enhanced elastic recoil, correction of ventilation perfusion mismatch, improved efficiency of respiratory musculature, and improved right ventricular filling. Questions that remain to be answered include duration of benefits, safety, and cost of LVRS. The National Heart, Lung, and Blood Institute and the Health Care Financing Administration have responded to the demand for more access to and information about LVRS by organizing both a national registry and controlled clinical trial of these procedures over a 7-year period. This multicenter trial intends to enroll patients with end-stage emphysema to compare methods of bilateral LVRS to maximal medical therapy.


[Effectiveness studies in the Italian Society of Occupational Medicine and Industrial Hygiene congresses (1989-2003)].
Knowledge of the results of studies on effectiveness of preventive interventions is a fundamental requirement in occupational medicine. The aim of this review was to identify Italian scientific production regarding this issue in the proceedings of the Italian Society of Occupational Medicine and Industrial Hygiene congresses over the last fifteen years. An initial selection of the communications on intervention effectiveness studies was performed on the basis of titles, aims, tables and figures of each single presentation. A further selection was made via full reading of the previously selected communications. The selected articles were classified by type of strategy discussed, production sector, study design and several other criteria. 108 studies were selected out of the 3215 papers (3.4%) published in the congress proceedings examined (1989-2003). More than half of these discussed technical control strategies. In the vast majority of cases, the study design was a pre- and post-evaluation of effectiveness, and the 6 (non-randomised) trials concerned vaccination programmes. Almost a quarter of the studies on accident prevention regarded the effectiveness of training programmes. Only 5 studies could be detected in Medline as articles later published in international journals. On the basis of the Italian Society of Occupational Medicine congress proceedings over the last 15 years, the percentage of communications concerning effectiveness of preventive interventions in occupational health was 3.4%. Intervention effectiveness papers published in congress proceedings seem to reveal a quite unexpected production of effectiveness evaluation studies. Nonetheless, recommendations need to be made to improve study design and to promote effective prevention and control strategies.


Central nervous system injury-induced repulsive guidance molecule expression in the adult human brain.
The repulsive guidance molecule (RGM) is involved in formation of the central nervous system during development by moderating the repulsion of growing axons. However, the role of RGM in adult central nervous system lesions remains to be clarified. To identify and determine RGM expression in adult brains with focal cerebral ischemia or traumatic brain injury and in neuropathologically unaffected control brains. Patients Twenty-one brains of patients with focal cerebral ischemia, 25 brains after traumatic brain injury, and 4 control brains. Main Outcome Measure Expression of RGM as assessed by immunohistochemical analysis. In normal brains, RGM expression was detected on the perikarya of some neurons, choroid plexus, smooth muscle and endothelial cells, oligodendrocytes, and myelinated white matter fibers. After focal cerebral ischemia and traumatic brain injury, RGM-immunopositive cells accumulated in lesional and perilesional areas. In hemorrhagic lesions, a massive accumulation of RGM-immunopositive cells was observed. During the first week after insult, RGM expression remained confined to neurons, smooth muscle and endothelial cells, and leukocytes infiltrating the lesion. Thereafter, with maturation of the lesion, we observed RGM expression by components of the developing scar tissue, such as fibroblastoid cells, reactive astrocytes, and a pronounced extracellular RGM deposition resembling neo-laminae. This is the first study of RGM in the human central nervous system. Following central nervous system injury, RGM, a novel, potent axonal growth inhibitor, is present in axonal growth impediments: the mature myelin, choroid plexus, and components of the developing scar.


Management of Fibrous Dysplasia of Proximal Femur by Internal Fixation Without Grafting: A Retrospective Study of 19 Patients.
This paper assesses whether treating patients with fibrous dysplasia of proximal femur by internal fixation with correction of the deformity, if present, without grafting is enough or not. This study is a retrospective study using patient's medical records, including analysis of 19 patients with fibrous dysplasia of proximal femur treated by internal fixation only and followed up between 2000 and 2017 for at least 2 years. Epidemiologic data, clinical manifestations, radiologic and histologic investigations, surgery, functional outcomes, and complications in these patients were analyzed. The study included 12 male patients and 7 female patients, with a mean age of 20.74 years. Of these, two patients presented with pathologic fractures, two presented with shepherd's crook deformity, and the remaining presented with hip pain and limping. Implants used for internal fixation were intramedullary nail in four patients, dynamic hip screw in eight patients, cannulated screws in four patients, broad dynamic compression plate in two patients, and narrow dynamic compression plate in one patient. The mean follow-up period was 53.58 months. Four patients had postoperative complications. The mean Musculoskeletal Tumor Society score was 27.63 points. The optimal management option for fibrous dysplasia of proximal femur is debatable. We suggest that internal fixation without grafting has a good local control and satisfactory functional long-term outcome.


A simplified cryogenic optical resonator apparatus providing ultra-low frequency drift.
A system providing an optical frequency with instability comparable to that of a hydrogen maser is presented. It consists of a 5 cm long, vertically oriented silicon optical resonator operated at temperatures between 1.5 K and 3.6 K in a closed-cycle cryostat with a low-temperature Joule-Thomson stage. We show that with a standard cryostat, a simple cryogenic optomechanical setup, and no active or passive vibration isolation, a minimum frequency instability of 2.5 × 10-15 at τ = 1500 s integration time can be reached. The influence of pulse-tube vibrations was minimized by using a resonator designed for low acceleration sensitivity. With reduced optical laser power and interrogation duty cycle, an ultra-low fractional frequency drift of -2.6 × 10-19/s is reached. At 3.5 K, the resonator frequency exhibits a vanishing thermal sensitivity and an ultra-small temperature derivative 8.5 × 10-12/K2. These are favorable properties that should lead to high performance also in simpler cryostats not equipped with a Joule-Thomson stage.


Application of Statistically Based Experimental Designs to Optimize Cellulase Production and Identification of Gene.
A natural bacterial strain identified as Bacillus amyloliquefaciens MBAA3 using 16S rDNA partial genome sequencing has been studied for optimization of cellulase production. Statistical screening of media components for production of cellulase by B. amyloliquefaciens MBAA3 was carried out by Plackett-Burman design. Plackett-Burman design showed CMC, MgSO4 and pH as significant components influencing the cellulase production from the media components screened by Plackett-Burman fractional factorial design. The optimum concentrations of these significant parameters were determined employing the response surface central composite design, involving three factors and five levels was adopted to acquire the best medium for the production of cellulase enzyme revealed concentration of CMC (1.84 g), MgSO4 (0.275 g), and pH (8.5) in media for highest enzyme production. Response surface counter plots revealed that middle level of MgSO4 and middle level of CMC, higher level of CMC and lower level of pH and higher level of MgSO4 with lower level of pH increase the production of cellulase. After optimization cellulase activity increased by 6.81 fold. Presence of cellulase gene in MBAA3 was conformed by the amplification of genomic DNA of MBAA3. A PCR product of cellulase gene of 1500 bp was successfully amplified. The amplified gene was conformed by sequencing the amplified product and sequence was deposited in the gene bank under the accession number KF929416. Response surface graph showing interaction effects between concentration of a CMC and MgSO4. b pH and CMC. c MgSO4 and pH.


[Validity of predictive power of the Adjusted Morbidity Groups (AMG) with respect to others population stratification tools.]
This work was performed in order to get objective elements of judgment that support the improvement of a national population morbidity grouper based in the Adjusted Morbidity Groups (AMG). The study compared the performance in terms of predictive power on certain health and resource outcomes, in between the AMG and several existing morbidity groupers (ACG®, Adjusted Clinical Groups and CRG®, Clinical Risk Group) used in some Autonomous Regions in Spain (Aragón, Canarias y Castilla y León). Cross-sectional analytical study in entitled/insured population with respect to rights of healthcare. Predictive capacity of the complexity weight obtained with the different stratification tools in the first year of the study period was evaluated using a simple classification method that compares the areas under the curves ROC for the following outcomes that occurred in the second year of the study period: Probability of death; probability of having at least one urgent hospital admission; total number of visits to hospital emergencies; total number of visits to primary care; total number of visits to hospital care and spending in pharmacy. The results showed that AMG complexity weight were good predictors for almost all the analyzed outcomes (AUC ROC>0.7; p<0.05), for the different Autonomous Regions and compared to ACG® or CRG®. Only for the outcome of visits to hospital emergencies in Aragon and Canarias; and visits to specialized care in Aragon, the predictive power was weak for all the compared stratification tools. GMA® is a population stratification tool adequate and as useful as others existing morbidity groupers.


Genetic and environmental risk structure of internalizing psychopathology in youth.
Internalizing disorders (IDs), consisting of syndromes of anxiety and depression, are common, debilitating conditions often beginning early in life. Various trait-like psychological constructs are associated with IDs. Our prior analysis identified a tripartite model of Fear/Anxiety, Dysphoria, and Positive Affect among symptoms of anxiety and depression and the following constructs in youth: anxiety sensitivity, fearfulness, behavioral activation and inhibition, irritability, neuroticism, and extraversion. The current study sought to elucidate their overarching latent genetic and environmental risk structure. The sample consisted of 768 juvenile twin subjects ages 9-14 assessed for the nine, abovementioned measures. We compared two multivariate twin models of this broad array of phenotypes. A hypothesis-driven, common pathway twin model reflecting the tripartite structure of the measures were fit to these data. However, an alternative independent pathway model provided both a better fit and more nuanced insights into their underlying genetic and environmental risk factors. Our findings suggest a complex latent genetic and environmental structure to ID phenotypes in youth. This structure, which incorporates both clinical symptoms and various psychological traits, informs future phenotypic approaches for identifying specific genetic and pathophysiological mechanisms underlying ID risk.


A lifetime modelled economic evaluation comparing pioglitazone and rosiglitazone for the treatment of type 2 diabetes mellitus in the UK.
Adding pioglitazone or rosiglitazone to existing therapy are alternative treatment options for patients with type 2 diabetes mellitus who have insufficient glycaemic control while receiving the maximal tolerated dose of metformin monotherapy. Our objective was to develop a lifetime model of type 2 diabetes mellitus and its sequelae in order to compare the costs and benefits of pioglitazone versus rosiglitazone in combination with metformin. A decision-analytic model employing a first order Monte Carlo simulation of a Markov process was constructed. The model incorporated surrogate outcome measures from a large randomised controlled trial (RCT) [n = 802] that compared the glycaemic and lipid control of pioglitazone and rosiglitazone monotherapy. These efficacy data were used with a recently validated and peer-reviewed UKPDS (UK Prospective Diabetes Study) algorithm to simulate the progression of these surrogate outcomes to final health outcomes, including quality of life (QOL) and mortality, and to calculate the risks of diabetic complications and death. The model perspective was of the UK NHS and included direct healthcare costs only (pounds, 2004/5 values). Patient outcomes measured in the model included life-expectancy (LE) and QALYs. The base-case analysis was run for 56-year-old male Caucasions with a haemoglobin A(1c) (HbA(1c)) of 7.57% and a body mass index of 33.14 kg/m(2). Patients treated with pioglitazone experienced a reduction in the total cholesterol to high-density lipoprotein-cholesterol (TC : HDL-C) ratio of 0.34, whereas the TC : HDL-C ratio increased by 0.65 in those receiving rosiglitazone (p < 0.001). The HbA(1c) profile was similar between the treatment groups (p = 0.13), as were other known risk factors for diabetes complications. The lifetime healthcare costs per patient estimated by the model were 9585 pounds for pioglitazone and 10,299 pounds for rosiglitazone. Patients treated with pioglitazone had a discounted LE of 8.83 years versus 8.79 years for those treated with rosiglitazone. Patients treated with pioglitazone also gained additional QALYs (6.8070 vs 6.7686). With improved health outcomes and lower costs, treatment with pioglitazone dominated rosiglitazone treatment. Evidence from the only large head-to-head RCT comparing rosiglitazone and pioglitazone suggests that more favourable changes in serum lipid profiles in patients treated with pioglitazone translate into improved health outcomes in terms of reduced morbidity and mortality and greater gains in QOL. In addition, this analysis indicates that treatment with pioglitazone is associated with lower costs than rosiglitazone. Therefore, in the UK, adjunctive pioglitazone may represent a cost-effective treatment choice for patients with type 2 diabetes who have insufficient glycaemic control while receiving the maximal tolerated dose of metformin monotherapy.


Prevalence of Overweight and Obesity in Jamaica From 2000 to 2016.
The prevalence of overweight and obesity in Jamaica has been steadily increasing over the past decade and is now a significant health issue. This paper focuses on the trends in the prevalence of overweight and obesity in Jamaica from 2000 to 2016. Overweight and obesity prevalence in adults increased from 43.8% in 2000 to 55.5% in 2016, from 34.2% in 2000 to 47.4% in 2016in adult males, and from 53.0% in 2000 to 63.6% in 2016 in adult females. In children/adolescents aged 10 to 19 years, the prevalence of obesity has doubled between 2000 and 2016. The data shows that the prevalence of overweight and obesity in children/adolescents increased from 5% in 2000 to 11.4% in 2016, from 4.4% in 2000 to 11.0% in 2016 in boys, and from 5.5% in 2000 to 11.9% in 2016 in girls.


Desipramine lowers tritiated para-aminoclonidine binding in platelets of depressed patients.
Platelet adrenergic receptor binding has been studied by several groups of investigators as a possible marker for depression and other psychiatric conditions. Although some of the findings have been discrepant, the results of the majority of studies that have used imidazoline compounds as ligands have confirmed elevated alpha 2-adrenergic receptor binding in depression. We have emphasized the advantages of obtaining platelet-purified plasma membranes and using tritiated para-aminoclonidine as the ligand of choice. By using "site-selective" concentrations of tritiated para-aminoclonidine, we have identified two high-affinity-binding sites of the platelet alpha 2-adrenergic receptor that appear to be upregulated in depression before treatment. Depressed patients were treated with desipramine hydrochloride for 6 to 8 weeks, and platelet binding was reassessed. Desipramine reduced binding to nearly normal levels at both site-selective concentrations of tritiated para-aminoclonidine. The concentrations of plasma catecholamines could play a role in the downregulation of binding at posttreatment. We discuss these findings in the context of platelet imidazoline-binding sites being a possible state-dependent marker for depression.


[POSITION STATEMENT ON OVERACTIVE BLADDER].
Bothersome urinary symptoms during the storage phase are common among women and men. These symptoms described as urinary urgency, frequency and nocturia with or without urge urinary incontinence may be caused by various pathologies including bladder overactivity. Diagnosis of an overactive bladder is based on the patient's clinical presentation after exclusion of other disorders that may cause these symptoms. The minimal requirements for a urological evaluation include medical history, physical examination and urinalysis. Behavioral therapies and medical therapy are the mainstay of treatment for an overactive bladder. While the use of minimally invasive procedures are reserved for patients not interested in medications or for those patients in whom symptoms were not improved by other therapies. Treatment outcome is evaluated by documentation of changes in symptoms, signs and quality of life. This position statement paper represents the approach of the Israeli Urological Association regarding the evaluation and treatment of overactive bladder syndrome.


Stability of visual acuity after the cessation of amblyopia treatment: review of the literature.
The treatment of amblyopia in children is frequently discussed in the literature. Less attention, however, has been given to the durability of the visual acuity results attained with therapy. The objective of this review is to conduct an in-depth analysis of the existing literature, on the stability of visual acuity following cessation of amblyopia treatment, and to identify any gaps in the literature, which could guide future investigations. There did not appear to be any one consistent risk factor affecting the stability of vision after cessation of amblyopia treatment. Most of the reviewed studies varied with respect to lengths of follow-up visits, patient population, and method of visual acuity assessment. There was also a generalized lack of standardization of visual acuity measurements in these previous investigations. Only one of the studies analyzed was a prospective design. The area of study in amblyopia is fraught with contradictions. It is obvious from this review that there exists uncertainty regarding the recurrence of amblyopia following treatment. Previous studies have failed to identify any common, predictive, influencing factors necessary for the maintenance of visual acuity after cessation of therapy. Also lacking is discussion on the potential role that therapy tapering plays in the recurrence of amblyopia following the cessation of treatment.


Characterization of H5N1 Influenza Virus Quasispecies with Adaptive Hemagglutinin Mutations from Single-Virus Infections of Human Airway Cells.
Transmission of avian influenza (AI) viruses to mammals involves phylogenetic bottlenecks that select small numbers of variants for transmission to new host species. However, little is known about the AI virus quasispecies diversity that produces variants for virus adaptation to humans. Here, we analyzed the hemagglutinin (HA) genetic diversity produced during AI H5N1 single-virus infection of primary human airway cells and characterized the phenotypes of these variants. During single-virus infection, HA variants emerged with increased fitness to infect human cells. These variants generally had decreased HA thermostability, an indicator of decreased transmissibility, that appeared to compensate for their increase in α2,6-linked sialic acid (α2,6 Sia) binding specificity and/or in the membrane fusion pH threshold, each of which is an advantageous mutational change for viral infection of human airway epithelia. An HA variant with increased HA thermostability also emerged but could not outcompete variants with less HA thermostability. These results provided data on HA quasispecies diversity in human airway cells.IMPORTANCE The diversity of the influenza virus quasispecies that emerges from a single infection is the starting point for viral adaptation to new hosts. A few studies have investigated AI virus quasispecies diversity during human adaptation using clinical samples. However, those studies could be appreciably affected by individual variability and multifactorial respiratory factors, which complicate identification of quasispecies diversity produced by selective pressure for increased adaptation to infect human airway cells. Here, we found that detectable HA genetic diversity was produced by H5N1 single-virus infection of human airway cells. Most of the HA variants had increased fitness to infect human airway cells but incurred a fitness cost of less HA stability. To our knowledge, this is the first report to characterize the adaptive changes of AI virus quasispecies produced by infection of human airway cells. These results provide a better perspective on AI virus adaptation to infect humans.


Development of an ecological assessment tool for a workplace physical activity program standard.
This project was undertaken to develop a Workplace Physical Activity Assessment Tool to evaluate workplace physical activity programs based on a standard of best practices indicated in the literature and by key stakeholders. The development of the Assessment Tool was structured on an ecological model for health and physical activity promotion and an occupational health and safety audit instrument. The project included a review and synthesis of pertinent literature, expert and stakeholder reviews, interrater reliability appraisals, and workplace consultations over three distinct study phases. The Assessment Tool was received positively by the expert reviewers (i.e., academics, policy makers, and practitioners) and revealed generally high interrater reliability. The Workplace Physical Activity Assessment Tool can be used to plan, implement, and evaluate physical activity programs in the workplace. Recommendations for future research are identified.


Effect of oral glucose supplementation on surface EMG during fatiguing dynamic exercise.
The aim of this study was to examine the effect of oral glucose supplementation on the surface electromyographic (sEMG) signal recorded during a dynamic, fatiguing exercise protocol. Five healthy subjects participated in the study. Blood glucose concentration and sEMG signals from five upper leg muscles were recorded during a cycling exercise performed at 70% VO2peak until task failure, on two separate occasions. Glucose was consumed at 15 minute intervals throughout one trial. The median frequency of the sEMG was observed to increase progressively throughout the exercise, with a greater increase in the with glucose condition. This is in direct contrast to the typical decrease in median frequency known to occur during a fatiguing isometric contraction. The result may indicate an increase in Na+ - K+ - AT Pase activity during fatiguing dynamic exercise resulting in an increase in muscle fiber membrane excitability due to membrane hyperpolarization.


Postfire response of flood-regenerating riparian vegetation in a semi-arid landscape.
Piles of large wood (LW) deposited by major floods in river corridors can interact with naturally occurring wildfires from uplands to impact the regeneration of riparian vegetation. This study examines the spatial and short-term temporal response of riparian vegetation and soil nutrients to fire along the Sabie River, South Africa, with special emphasis on the effects of burned LW piles. At the study site there were 112 species of plants recorded with 28% of species restricted to the burned plots. As expected, vegetation cover was significantly lower in burned plots as compared with the unburned plots 12 months postfire. There was a significant influence of LW on species richness with fewer species recorded in the LW plots. For both fire and LW treatments, plant cover showed a significant change over three years. After an initial increase from 12 to 24 months (postfire) there was a decline in plant cover after 36 months. Species community composition was distinctly different between burned and unburned plots 12 months postfire, and the presence of LW affected species composition for burned plots but not for unburned ones. Time series ordination of LW plots highlighted the changes in species composition over the three years of sampling. Of trees with accumulations of LW within 5 m of their base, 48% had been killed by fire as compared to only 4% with no LW accumulations in close proximity. Soil-available P was significantly higher in the burned plots and even higher with burned LW while there were no effects on soil total N. There was also a significant positive trend between available P in soils and plant vegetation cover. Soil-exchangeable K was also significantly higher and total C significantly lower in the burned and LW plots. Burned plots also had significantly higher soil electrical conductivity (EC) and soil pH. The patchy nature of the studied fire, whose complexity is exacerbated by the distribution of flood deposited LW, acted to create a mosaic of alternate successional states as the riparian community recovers from flooding and the subsequent fire. We suspect that the resultant heterogeneity will increase ecosystem resilience by providing flexibility in the form of more options for a system response to subsequent disturbances.


Early Seizures Are Predictive of Worse Health-Related Quality of Life at Follow-Up After Intracerebral Hemorrhage.
Early seizures are a common complication of intracerebral hemorrhage, occurring in ~10% of patients. However, the independent effect of early seizures on patient outcomes, particularly health-related quality of life, is unclear. Without a potential benefit to patient outcomes, the widespread use (~40%) of prophylactic seizure medications has no reasonable chance of improving patient outcomes. We tested the hypothesis that health-related quality of life at follow-up is different between patients with and without early seizures (and secondarily, with nonconvulsive status epilepticus) after intracerebral hemorrhage. Patients with intracerebral hemorrhage were enrolled in an observational cohort study that prospectively collected clinical data and health-related quality of life at follow-up. Academic medical center. One-hundred thirty-three patients whose health-related quality of life was assessed 3 months after intracerebral hemorrhage onset. Health-related quality of life was obtained at 3 months after intracerebral hemorrhage onset. T Scores of health-related quality of life were modeled with multivariable linear models accounting for severity with the intracerebral hemorrhage Score and hematoma location. Health-related quality of life was measured with National Institutes of Health Patient Reported Outcomes Measurement Information System/Neuroquality of life, expressed in T Scores (U.S. normal 50 ± 10). The modified Rankin Scale (a global measure) was a secondary outcome. There were 12 patients (9%) with early seizures. T Scores of health-related quality of life at follow-up were lower (worse) in patients with early seizure compared with patients without an early seizure (44 [32.75-51.85] vs 30.25 [18.9-39.15]; p = 0.04); results for other domains of health-related quality of life were similar. The association persisted in multivariable models. There was no association between early seizures and prophylactic seizure medications (p = 0.4). Results for patients with nonconvulsive status epilepticus were similar. There was no association between early seizures and the modified Rankin Scale at 3 months. Early seizures and nonconvulsive status epilepticus were associated with lower health-related quality of life at follow-up in survivors of intracerebral hemorrhage.


Note: Studies on target placement in TE(111) cylindrical cavity of electron cyclotron resonance x-ray source for the enhancement of x-ray dose.
X-ray source based on electron cyclotron resonance principle has been constructed using TE(111) cylindrical cavity. At present the device is used to provide low energy x-ray field for thermoluminescent dosimeter badge calibration. Theoretical and experimental studies on the effect of target placement inside the TE(111) cylindrical cavity for enhancing the x-ray output are carried out and the results are presented in this note. Optimum target location is identified by theoretical analysis on the electric field distribution inside the cavity using MICROWAVE STUDIO program. By modifying the magnetic field configuration, the resonance region is shifted to the optimum target location. The microwave transmission line is upgraded with a three stub tuner which improves the microwave coupling from the source to the target loaded cavity. Molybdenum target is located at a radial distance of 2.5 cm from the cavity center and the x-ray dose rate is measured at 20 cm from the exit port for different microwave power. With the introduction of the target, the x-ray output has improved nearly from 70% to 160% in the microwave power of 150-500 W.


Using an In-Sample Addition of Medronic Acid for the Analysis of Purine- and Pyrimidine-Related Derivatives and Its Application in the Study of Lung Adenocarcinoma A549 Cell Lines by LC-MS/MS.
Intracellular purine- and pyrimidine-related derivatives are vital molecules for preserving genetic information and are essential for cellular bioenergetics and signal transduction. This study developed a practical liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying intracellular purine- and pyrimidine-related derivatives. To solve the distorted peak shape related to di- and triphosphate nucleotides, in-sample addition of medronic acid and ammonium phosphate was performed. Using the BEH-amide column, the results showed that adding 0.5 mM medronic acid to the sample significantly improved the peak shape without causing an obvious ion suppressive effect. Method validation confirmed that the coefficients of determination (R2) values for linearity evaluation were above 0.94 for all analytes. The intraday and interday accuracies ranged from 85.1 to 128.4%, with the precision below 16.6%. The validated method was successfully applied in characterizing the alterations of purine- and pyrimidine-related derivatives in the A549 cell line with perturbed mitochondrial fission or blockade of the electron transport chain. Collectively, this study demonstrates that the strategy of in-sample medronic acid addition is effective in improving the quantification of intracellular purine- and pyrimidine-related derivatives. We believe that our proposed platform can facilitate the development of novel drugs targeting purine and pyrimidine metabolism in the future.


Fiber retention and papilla preservation technique in the treatment of infrabony defects: a microsurgical approach.
The enhanced visual perception and illumination of an operative microscope improve surgical techniques in terms of flap incision, quality of root debridement, and suturing. The aim of this study is to describe microsurgical flap access for the treatment of periodontal pockets associated with shallow to moderate bony defects in the esthetic zone of the mouth. This technique combines preservation of the still-attached gingival fibers and maintenance of the body of the interproximal papilla. The results in terms of attachment level gain and residual pocket depth show that the described microsurgical approach helps to minimize marginal tissue recession and improve esthetics in the treatment of shallow to moderate bony defects.


Investigation of keratinophilic fungi from soils in western Australia a preliminary survey.
In order to determine which species of geophilic dermatophytes were present in Western Australian soils 299 samples were investigated. These samples were collected from a range of locations, 208 towns throughout the state and 91 samples from the Perth Metropolitan area. Most samples were collected from areas frequented by people and animals, such as home gardens, parks and animal yards. Of the total 299 soils, 271 (90.6%) yielded keratinophilic fungi. A total of 181 dermatophytes were isolated, and there were 205 isolations of other keratinophilic fungi. Microsporum gypseum (30.7%) was the most prevalent dermatophyte recovered from soil followed by Microsporum cookei (21.7%) and then Trichophyton ajelloi (8.0%). No other dermatophytes were recovered. Chrysosporium indicum was the most common of all the keratinophilic fungi and was isolated from 50.1% of the samples. Mixed growth was obtained from 33.5% of the soil samples.


A Novel Validated Breast Aesthetic Scale.
Breast aesthetics impacts patients' quality of life after breast reconstruction, but patients and surgeons frequently disagree on the final aesthetic evaluation. The need for a comprehensive, validated tool to evaluate breast aesthetics independently from the patient motivated this study. The 13-item Validated Breast Aesthetic Scale was developed after several internal meetings, and worded to be understood by a nonspecialist. Three items are common for both breasts, with the remaining being side-specific. To test the internal consistency of the scale subitems, postoperative photographs after different breast reconstruction techniques were graded by a six-member panel. To test interrater and intrarater correlation across time, four physicians evaluated the results of abdominally based breast reconstructions following nipple-sparing mastectomies. Graded aesthetic outcomes of 53 patients showed that the Cronbach alpha of the subitems of the scale was 0.926, with no single item that, if excluded, would increase it. Twenty-two patients underwent aesthetic outcomes grading at four different time points. The mean overall appearance was 3.71 ± 0.62. The mean grade for overall nipple appearance was 4.0 ± 0.57. The coefficient alpha of the panel overall aesthetic grade across different time points was 0.957; whereas intragrader reliability for graders 1 through 4 individually showed alpha coefficients of 0.894, 0.9, 0.898, and 0.688, respectively. Similar results were found for the other items of the scale. The proposed aesthetic scale evaluates different aspects of the breast reconstruction aesthetic result with excellent internal consistency among its subitems. Grading by a gender-balanced, diverse four-member panel using postoperative photographs showed higher reliability and reproducibility compared to single graders.


Nonadherence after pediatric renal transplantation: detection and treatment.
Nonadherence is a problem in adolescents and young adults. Risk factors are classified as those of the individual, family, health-care-system, or community. I present the latest reports and how to tackle nonadherence. Nonadherence risk is independent of one's origin in a high-poverty or low-poverty neighborhood or having private or public insurance in respect to African Americans. Females with male grafts have higher graft-failure risks than do males. Female recipients aged 15-24 with grafts from female donors have higher graft-failure risk than do males. In study of nonadherence risks, such findings must be taken into account. Antibody-mediated rejection is seen in nonadherence. The sirolimus and tacrolimus coefficient of variation is associated with nonadherence, donor-specific antibodies, and rejection. Adolescents had electronically monitored compliance reported by e-mail, text message or visual dose reminders and meetings with coaches. These patients had significantly greater odds of taking medication than did controls. Transition programs have an impact on renal function and rejection episodes. Individual risk factors are many, and methods for measuring nonadherence exist. Each transplant center should have a follow-up program to measure nonadherence, especially in adolescence, and a transition program to adult care.


Access to public mental health services: determinants of population coverage.
This study examined factors that affect access to Veterans Administration mental health services. Data from national Veterans Affairs databases and the 1990 Decennial Census were used to estimate rates of Veterans Affairs mental health service use in each US county (n = 3,156) among all US veterans and in three subpopulations defined by eligibility and clinical status. Independent variables examined in standard multivariate analyses and using hierarchical linear modeling techniques included county-level sociodemographic characteristics (age, race, and income); "unmanaged" service system characteristics (those not directly controlled by Veterans Affairs program managers, eg, distance from residence to Veterans Affairs and to non-Veterans Affairs services, local supply of non-Veterans Affairs services); and "managed" service system factors (those directly controlled by Veterans Affairs program managers, eg, per capita Veterans Affairs funding level and the efficiency of Veterans Affairs service delivery). Altogether, 2.0% of US veterans used Veterans Affairs mental health services. More than one third (36%) of the variance in utilization was explained by sociodemographic factors; 8% was explained by unmanaged service system factors and 7% was explained by managed service system factors, with variations among subgroups. Substitution effects were demonstrated between Veterans Affairs and non-Veterans Affairs systems and appeared to be diagnosis-specific. Both per capita funding levels and efficient service delivery were significantly associated with increased access to mental health services. Implications for health system performance assessment and management are discussed.


Long-term effectiveness in patients previously treated with cladribine tablets: a real-world analysis of the Italian multiple sclerosis registry (CLARINET-MS).
The CLARINET-MS study assessed the long-term effectiveness of cladribine tablets by following patients with multiple sclerosis (MS) in Italy, using data from the Italian MS Registry. Real-world data (RWD) from Italian MS patients who participated in cladribine tablets randomised clinical trials (RCTs; CLARITY, CLARITY Extension, ONWARD or ORACLE-MS) across 17 MS centres were obtained from the Italian MS Registry. RWD were collected during a set observation period, spanning from the last dose of cladribine tablets during the RCT (defined as baseline) to the last visit date in the registry, treatment switch to other disease-modifying drugs, date of last Expanded Disability Status Scale recording or date of the last relapse (whichever occurred last). Time-to-event analysis was completed using the Kaplan-Meier (KM) method. Median duration and associated 95% confidence intervals (CI) were estimated from the model. Time span under observation in the Italian MS Registry was 1-137 (median 80.3) months. In the total Italian patient population (n = 80), the KM estimates for the probability of being relapse-free at 12, 36 and 60 months after the last dose of cladribine tablets were 84.8%, 66.2% and 57.2%, respectively. The corresponding probability of being progression-free at 60 months after the last dose was 63.7%. The KM estimate for the probability of not initiating another disease-modifying treatment at 60 months after the last dose of cladribine tablets was 28.1%, and the median time-to-treatment change was 32.1 (95% CI 15.5-39.5) months. CLARINET-MS provides an indirect measure of the long-term effectiveness of cladribine tablets. Over half of MS patients analysed did not relapse or experience disability progression during 60 months of follow-up from the last dose, suggesting that cladribine tablets remain effective in years 3 and 4 after short courses at the beginning of years 1 and 2.


[Capacitive requirement for acute in-patient care of patients with psychosomatic diseases in bavaria].
Estimations of the requirement for acute in-patient care of patients with psychosomatic diseases in Bavaria have to rely on respective data on their incidence and prevalence as valid requirement data are missing. The required capacity of in-patient beds depends on several, inconsistently figured parameters: hospitalization rate, length of stay, occupancy rate. Based on conservative assumptions the hospitalization rate was calculated to be at least 1.3 admissions per 1000 and for adequate treatment the average length of stay should not be limited to less than 50 days. In order to avoid unnecessary delay of treatment a realistic occupancy rate has to be 90 %. Thus the minimal capacity for in-patient care is assessed to be 2453 beds. At present patients with psychosomatic diseases in Bavaria receive in-patient treatment in psychosomatic departments of general hospitals, hospitals and rehab clinics of psychosomatic and psychotherapeutic medicine, and in hospitals of psychiatry and psychotherapy, in each with a different focus. When the expertise was drafted these acute care and rehab hospitals provided some 2500 beds - with only 76 beds in general hospitals. For quality assessment of the available beds for in-patient care and future planning minimal standards of structural quality have to be consented. At present it is not possible to make a clear and substantial distinction between the treatment for patients with psychosomatic diseases in acute-care hospitals and in psychosomatic rehab clinics respectively. Thus, the necessary in-patient rehab capacity can only be assessed roughly. The existing pluralism of the in-patient care providing system for patients with psychosomatic diseases is considered to be appropriate for different needs of this patient group. In the future excellent care for this patient group will acknowledge options for a more flexible and interconnected care-providing system. This is a publication of the complete expertise by the project group "Acute In-patient Care for Patients with Psychosomatic Diseases in Bavaria" which has been handed to the Bavarian Ministry of Social Affairs in December 1999.


Reproductive choices and intrafamilial communication in neurogenetic diseases with different self-estimated severities.
Low uptake of presymptomatic testing and medically assisted reproduction in families impacted by neurogenetic diseases prompted us to investigate how reproductive options are considered and whether there is a relationship with perceived severity of the disease. We hypothesised that self-estimated severity would influence opinion on reproductive options and that prenatal/preimplantation diagnosis would be a motivation to inform relatives about their risk. We invited people impacted by neurogenetic diseases to evaluate the severity of their familial disease using analogic visual scales and to answer questionnaires about reproductive choices and intrafamilial communication. We compared answers between diseases and with the perceived severity of each disease. We analysed 562 questionnaires. Participants were impacted by Huntington disease (n=307), spinocerebellar ataxias (n=114), Steinert myotonic dystrophy (n=82) and amyotrophic lateral sclerosis/frontotemporal dementia (n=59). Self-estimated severity differed between pathologies (p<0.0001). Overall, participants considered prenatal diagnosis (78.0±34.4 out of 100) and preimplantation diagnosis (75.2±36.1 out of 100) justified more than termination of pregnancy (68.6±38.5 out of 100). They were less in favour of gamete donation (48.3±39.8 out of 100) or pregnancy abstention (43.3±40.3 out of 100). The greater the perceived severity of the disease, the more reproductive options were considered justified, except for gamete donation. Prenatal/preimplantation diagnosis was a motivation to inform relatives for only 55.3% of participants (p=0.01). Self-estimated severity minimally impacts opinions towards reproductive options. Medically assisted reproduction procedures are rarely sought and do not motivate familial communication.


The risk of transmission of Crimean-Congo hemorrhagic fever virus from human cases to first-degree relatives.
To determine the infectivity of Crimean-Congo hemorrhagic fever (CCHF) virus via routine contacts between serologically confirmed cases and their close relatives from May 2005 up to March 2006, 79 serum samples of 57 close relatives of 12 newly diagnosed serologically confirmed CCHF cases in the Sistan-va-Baluchestan province of Iran were tested for IgG and IgM antibodies against CCHF virus using the enzyme-linked immunosorbent assay technique. Nine levels of contacts were considered: percutaneous contact with the patient's blood, cutaneous contact with the patient's blood, cutaneous contact with non-sanguineous body fluids, cutaneous contact with the patient's skin, sexual contact, eating at the same table, being a roommate of the patient, being a housemate of the patient, and living with the patient in the same building. Only one out of 57 relatives was positive for anti-CCHF IgG (1.8%, 95% confidence interval 0.0 to 9.8%). Thus, the infectivity of the virus via usual routine contacts with patients appears to be low.


Genoarchitecture of the Early Postmitotic Pretectum and the Role of Wnt Signaling in Shaping Pretectal Neurochemical Anatomy in Zebrafish.
The pretectum has a distinct nuclear arrangement and complex neurochemical anatomy. While previous genoarchitectural studies have described rostrocaudal and dorsoventral progenitor domains and subdomains in different species, the relationship between these early partitions and its later derivatives in the mature anatomy is less understood. The signals and transcription factors that control the establishment of pretectal anatomy are practically unknown. We investigated the possibility that some aspects of the development of pretectal divisions are controlled by Wnt signaling, focusing on the transitional stage between neurogenesis and histogenesis in zebrafish. Using several molecular markers and following the prosomeric model, we identified derivatives from each rostrocaudal pretectal progenitor domain and described the localization of gad1b-positive GABAergic and vglut2.2-positive glutamatergic cell clusters. We also attempted to relate these clusters to pretectal nuclei in the mature brain. Then, we examined the influence of Wnt signaling on the size of neurochemically distinctive pretectal areas, using a chemical inhibitor of the Wnt pathway and the CRISPR/Cas9 approach to knock out genes that encode the Wnt pathway mediators, Lef1 and Tcf7l2. The downregulation of the Wnt pathway led to a decrease in two GABAergic clusters and an expansion of a glutamatergic subregion in the maturing pretectum. This revealed an instructive role of the Wnt signal in the development of the pretectum during neurogenesis. The molecular anatomy presented here improves our understanding of pretectal development during early postmitotic stages and support the hypothesis that Wnt signaling is involved in shaping the neurochemical organization of the pretectum.


ABA mediates PEG-mediated premature differentiation of root apical meristem in plants.
Root apical meristem (RAM) is central for indeterminate growth of plant roots and in sensing environmental stimuli, such as water status. Recently, we reported that PEG8000-simulated mild and moderate osmotic stress induces premature differentiation of RAM, which is a conserved adaptive mechanism in higher plants to cope with water stress. Microarray data analysis revealed that the ABA signaling pathway may be involved in water stress-induced RAM premature differentiation. Here we showed that in wheat, ABA contents increased under water stress with the highest level of ABA in the RAM. Exogenous ABA also induces RAM premature differentiation in both wheat and Arabidopsis plants. Further genetic analysis revealed that loss of function mutations in ABA2 and ABA receptors significantly reduced the level of root tip swelling and RAM premature differentiation in response to PEG-simulated water stress. Together, the results suggest that ABA participates in regulation of PEG-mediated premature differentiation of RAM.


Routine serum lipid analysis in New Zealand.
For two years pairs of serum specimens with a wide range of cholesterol and triglyceride concentrations were regularly dispatched each month to all New Zealand medical laboratories known to measure blood lipids. Four weeks after specimen dispatch each laboratory received a report which displayed all results along with the overall means, standard deviations, and results from "reference laboratories". Six-monthly summaries were prepared for each laboratory in which the previous 12 results were compared with the corresponding "target values" by regression analysis. This allowed classification of inaccuracy into one or more of three categories. Random error (imprecision) explained most of the discrepancies, but systematic errors also contributed strongly to the observed interlaboratory variation. No single class of laboratories performed significantly differently from any others. Approximately 60 percent of the 16000 cholesterol analyses done each month in New Zealand, and 40 percent of the 10000 triglyceride analyses, are performed with precision thought to be adequate for clinical usage.


Development of an UPLC mass spectrometry method for measurement of myofibrillar protein synthesis: application to analysis of murine muscles during cancer cachexia.
Cachexia, characterized by skeletal muscle mass loss, is a major contributory factor to patient morbidity and mortality during cancer. However, there are no reports on the rate of myofibrillar protein synthesis (MPS) in skeletal muscles that vary in primary metabolic phenotype during cachexia, in large part because of the small-size muscles and regional differences in larger muscles in the mouse. Here, we describe a sensitive method for measurement of MPS and its application to analysis of MPS in specific muscles of mice with (Apc(Min/+)) and without (C57BL/6) cancer cachexia. Mice were injected with a loading dose of deuterated phenylalanine (D5F), and myofibrillar proteins were extracted from skeletal muscles at 30 min. The relative concentrations of D5F and naturally occurring phenylalanine (F) in the myofibrillar proteins and the amino acid pool were quantified by ultra-performance liquid chromatograph (UPLC) mass spectrometry (MS). The rate of MPS was determined from D5F-to-F ratio in the protein fraction compared with the amino acid pool. The rate of MPS, measured in 2-5 mg of muscle protein, was reduced by up to 65% with cachexia in the soleus, plantaris, diaphragm, and oxidative and glycolytic regions of the gastrocnemius. The rate of MPS was significantly higher in the oxidative vs. glycolytic gastrocnemius muscle. A sufficiently sensitive UPLC MS method requiring a very small amount of muscle has been developed to measure the rate of MPS in various mouse muscles. This method should be useful for studies in other animal models for quantifying effects of cancer and anti-cancer therapies on protein synthesis in cachexia, and particularly for analysis of sequential muscle biopsies in a wide range of animal and human studies.


Reversed diastolic flow in the uterine artery - a new Doppler finding related to placental insufficiency?
Increased uterine artery pulsatility and resistance indices with or without notching of the waveform have been associated with an increased risk of pre-eclampsia and fetal growth restriction. However, reversed diastolic flow in the uterine artery has not previously been reported. We present two high-risk obstetric cases complicated by severe placental insufficiency: pre-eclampsia followed by eclampsia in one case and intrauterine growth restriction with abnormal cardiotocography in the other. Doppler studies of the uterine arteries revealed reversed diastolic flow in both cases. The pathophysiology and potential implications are discussed.


The role of the victim-offender relationship on psychological distress among Latinx women: A betrayal trauma perspective.
The current study expands the knowledge within the betrayal trauma literature by applying this conceptualization to the victimization of Latinx women, a generally understudied minority group in the United States. Under the betrayal trauma framework, this study focuses on the victim and perpetrator relationship of Latinx women to examine trauma-related psychological distress outcomes, including depression, anger, dissociation, and anxiety. Using data from the Sexual Assault Among Latinas Study on 2,000 adult Latinx women in the United States, findings examine the victim-perpetrator relationship of the Latinx women who experienced victimization (n = 870). Ordinary least squares regressions were conducted with the Trauma Symptom Inventory scales of depression, anger, dissociation, and anxiety as the dependent variables, resulting in four regression models. A sequential regression including the interaction terms was then completed for each of the TSI scale outcomes to account for possible moderation between cultural variables and victim-perpetrator relationships. Linear models show that childhood betrayal trauma and total victimization significantly associate with greater psychological distress, including depression, anger, dissociation, and anxiety. Interactions effects were significant for anxiety, showing a stronger relationship between childhood family-perpetrated victimization for highly enculturated women while the opposite was found for family-perpetrated victimization in adulthood where low-enculturated women had a stronger relationship to anxiety. The study findings support the betrayal trauma theory among Latinx women by showing that the closeness in relationship between the victim and the perpetrator for childhood victimization was associated with greater psychological distress above and beyond the impact of other perpetrator-victim relationships. This effect remained significant even when accounting for the total lifetime victimization. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Getting the data in: three year experience with a pediatric electronic medical record system.
The Clinician's Workstation (CWS) has provided the full-functionality of an on-line electronic patient record for outpatient pediatric clinics over the past 3 years. The implementation of the CWS built upon a substantial effort in integration of data from various sources. This paper addresses the subsequent design issues which had to be resolved in order to enable both physician and transcriptionist-driven data entry and retrieval, notably selecting a feasible mixture of controlled vocabulary and free text. Some of the consequences of these design decisions on clinical care, clinical education, clinical and basic research are reviewed with examples from the last three years.


Measuring the true success of laparoscopic pyeloplasty.
Laparoscopic pyeloplasty (LP) is a highly successful minimally invasive management option for ureteropelvic junction obstruction (UPJO) with success rates equaling or surpassing open repair. Definitions of success have varied greatly among reports of series in the literature. We propose that true success or failure be strictly defined by resolution of obstruction on objective physiologic testing (diuretic renography or Whitaker testing) and accordingly present our results. We prospectively gathered data on all LP from December 2001 to November 2006. Ninety-two patients have matured to follow-up testing (> 3 months). Primary uncomplicated procedures were completed in 62/92 (67%) while secondary and/or complex repairs were performed in 30/92 (33%). Rigorous follow-up with physiologic testing was performed postoperatively. Patients with equivocal diuretic renal scans were evaluated with Whitaker pressure-flow studies. The subjective symptom score was assessed for our first 47 patients using a visual analog scale (VAS). Treatment in patients who lacked objective evidence of resolution of UPJO was considered a failure. The mean age of the cohort was 39 years (range 18-69 yrs). Average operating room time was 250 minutes (range 138-488 min), and estimated blood loss was 63 mL (range 10-500 mL). Average hospital length of stay was 1.2 days (range 1-6 d). Crossing vessels were identified in 47/92 (51%) patients. Overall mean follow-up was 13 months (range 2-54 months). There were no intraoperative complications and three perioperative complications. Overall, 85/92 (92%) patients were found to have resolution of UPJO on postoperative physiologic testing. The primary uncomplicated cohort success rate was 98%, while that for the secondary or complex repair cohort was 80%. The mean overall VAS pain score was 84%. Objective physiologic testing should be used as the measurement of true success after LP. A uniform definition of success will allow improved comparison of results with literature series and comparison with alternative management modalities.


Glycoprofiling of bifidobacterial consumption of human milk oligosaccharides demonstrates strain specific, preferential consumption of small chain glycans secreted in early human lactation.
The molecular basis by which human breast milk supports the development of a protective intestinal microbiome in infants is unknown. After lactose and lipids, human milk oligosaccharides (HMOs) are quantitatively the third largest and most diverse component of breast milk. In this work, glycomic profiling of HMO consumption by bifidobacteria using Fourier transform ion cyclotron resonance mass spectrometry reveals that one species, Bifidobacterium longum biovar infantis ATCC 15697, an isolate from the infant gut, preferentially consumes small mass oligosaccharides, representing 63.9% of the total HMOs available. These HMOs were detected in human breast milk at the onset and constantly through the first month of lactation by use of high performance liquid chromatography-chip time-of-flight mass spectrometry. Further characterization revealed that strain ATCC 15697 possesses both fucosidase and sialidase activities not present in the other tested strains. This work provides evidence that these small mass HMOs are selectively metabolized by select bifidobacterial strains and represent a potential new class of bioactive molecules functioning as prebiotics to facilitate a protective gut colonization in breast-fed newborns.


Adoptive therapies: quo vadis?
The success of adoptive immunotherapy using interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells in treating a percentage of patients with melanoma and renal cell carcinoma has provided impetus to research into both how to optimize this treatment as well as approaches into making immunotherapy in general more successful. As the question on how to optimize IL-2 dose, schedule, cell culture conditions, and other specifics of IL-2 plus LAK therapy are addressed in clinical trials, other approaches suggested by data from in vitro, animal, and the clinical studies using IL-2 are emerging into clinical trials. (table; see text) These include two major areas of focus at the present time: (1) the use of IL-2 +/- LAK in combination with a variety of agents which have been shown to be synergistic with it, including other biological response modifiers (such as interferons), agents which may act both as interferon inducers as well as by other mechanisms (poly-IC:LC and flavone-8-acetic acid), and chemotherapeutic agents (especially cyclophosphamide, doxorubicin and agents which have some activity against the disease being treated such as DTIC for melanoma), and (2) various approaches aimed at inducing and expanding tumor-specific immune cells which appear to have greater antitumor activity than LAK cells and which may be major contributors to the antitumor efficacy of IL-2 therapy. These approaches also have the potential benefit of inducing memory cells with a resultant long-term immune antitumor response. Approaches aimed at activating specific antitumor immune cells include the use of IL-2-expanded infiltrating lymphocytes from tumors, exposure of peripheral blood cells cultured in IL-2 to tumor cells to hopefully expand those with a specific antitumor response, and the use of tumor cell vaccines in conjunction with IL-2. In addition to approaches using activated and expanded LAK effectors or specific T cells, the potential role of activated (e.g. by gamma interferon) and expanded (e.g. by macrophage colony stimulating factor) macrophages in the adoptive immunotherapy of cancer remains an area of ongoing exploration both in preclinical studies and clinical trials. As a greater understanding of the antitumor mechanisms of IL-2 and LAK therapy and other forms of adoptive immunotherapy is achieved, therapeutic approaches can be defined which will maximize the ability to mediate the immune destruction of tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)


Regulation of integrin activation through the B-cell receptor.
Effective immune surveillance is absolutely dependent on the migration of lymphocytes throughout the body and on their successful recognition of specific antigens. Both of these functions rely on the capacity of integrins that are expressed on the surface of lymphocytes to respond in a highly regulated manner to a variety of chemokines and antigens. This Commentary is primarily concerned with the role of the B-cell integrins LFA-1 and VLA-4 in the antigen-recognition process, and summarises what is currently known about the molecular mechanisms of ;inside-out' integrin activation in response to B-cell-receptor stimulation. Recent investigations have identified Vav, PI3K and small GTPases as crucial regulators of the inside-out activation of B-cell integrins. These observations are of particular interest as they allude to an underlying mechanism by which B-cell-receptor-mediated signalling is linked to cytoskeleton reorganisation and subsequent integrin activation.


[Endocarditis or bacteremia caused by Streptococcus bovis and colorectal neoplasms].
Streptococcus bovis is a relatively frequent causative agent of endocarditis or bacteriaemia, particularly in the elderly. In the past S. bovis has often been incompletely or even falsely classified. For therapeutic and prognostic reasons it is important to classify this agent exactly with biochemical methods even in the routine laboratory. Endocarditis or bacteriaemia due to S. bovis are often seen in conjunction with malignant, potentially malignant or benign colorectal neoplasias. After endocarditis or bacteriaemia due to S. bovis thorough investigation of colon and rectum is indicated. On the other hand, in presence of fever in patients with colorectal tumors, S. bovis bacteriaemia or endocarditis must be considered. The available literature is inconclusive on the question whether, after S. bovis endocarditis or bacteriaemia with initially normal colorectal findings, examination of the upper gastrointestinal tract and periodic inspection of the colon is needed. Up to now there has been no satisfactory explanation for the concomitant occurrence of endocarditis or bacteriaemia due to S. bovis and colorectal neoplasia.


Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning.
The hippocampus is a key structure involved in learning and remembering spatial information. However, the extent to which hippocampal region CA2 is involved in these processes remains unclear. Here, we show that chronically silencing dorsal CA2 impairs reversal learning in the Morris water maze. After platform relocation, CA2-silenced mice spent more time in the vicinity of the old platform location and less time in the new target quadrant. Accordingly, behavioral strategy analysis revealed increased perseverance in navigating to the old location during the first day and an increased use of non-spatial strategies during the second day of reversal learning. Confirming previous indirect indications, these results demonstrate that CA2 is recruited when mice must flexibly adapt their behavior as task contingencies change. We discuss how these findings can be explained by recent theories of CA2 function and outline testable predictions to understand the underlying neural mechanisms. Demonstrating a direct involvement of CA2 in spatial learning, this work lends further support to the notion that CA2 plays a fundamental role in hippocampal information processing.


Two-State Folding Energy Determination Based on Transition Points in Nonequilibrium Single-Molecule Experiments.
Many small protein domains or nucleic acid structures undergo two-state unfolding-refolding transitions during mechanical stretching using single-molecule techniques. Here, by applying the Jarzynski equality (JE), we analytically express the folding energy of a molecule as a function of the experimentally measured transition points ξ* obtained with two typical time-varying mechanical constraints: the force constraints F(t) and the position constraints R(t) of a Hookian spring attached to one end of the molecule. Compared to previous applications of JE based on the integration of accurately measured force-extension curves of a tether that typically contains the molecule of interest and handles, our approach just needs to accurately measure a single data point. In the case of the F(t) process, the calculation is handle-independent. The broad applications of the theory are demonstrated by measuring the folding energies of a DNA hairpin, a DNA G-quadruplex, and the titin I27 domain based on transition forces using magnetic tweezers.